1. Field of the Invention
The present invention relates to an apparatus and method for treatment of the heart and, more particularly, to an apparatus and method for providing a therapeutic sub-threshold electrical current to the heart.
2. Discussion of the Related Art
A wide range of therapies is available for the treatment of cardiac tissue damage, heart failure and for treatment of the specific underlying disease processes. Most of these therapies may be classified as drugs, surgical intervention, or cardiac assist devices. The cardiac assist devices assist the heart in pumping function to relieve the heart of stresses during the healing process. If a condition is caused by coronary disease or is exacerbated by conduction defects, available therapies include either bypass surgery or angioplasty in the case of the former, or pacemaker therapy in the case of the latter. The above-mentioned damage and diseases as well as other factors set in motion the condition known as congestive heart failure (CHF). Although therapies have addressed treating specific indications, few therapies address the problem of tissue remodeling.
Tissue remodeling refers to the histological alteration of tissue over time. Remodeling may include histological and/or biochemical changes at the tissue, cellular and molecular levels. Tissue remodeling can be either beneficial or degenerative to a patient. Tissue remodeling is degenerative when histologically and/or biochemically normal tissue is altered in such a way that the tissue no longer functions properly. Degenerative tissue remodeling may occur progressively in patients suffering from congestive heart failure or atrial fibrillation. In those patients, the resulting remodeling adversely affects the heart's performance and exacerbates the deteriorating condition of the heart. Tissue remodeling is beneficial when a histologically and/or biochemically abnormal tissue is reverted to a more normal histology and/or biochemistry.
Recently, one aspect of degenerative remodeling due to the progression of CHF has been identified as the breakdown in the collagen of the extra-cellular matrix. The extra-cellular matrix is the external structure between the cells in the heart that primarily consists of a matrix of type I collagen and fibrils. This matrix is connected to the cytoskeletal myofibrils within the myocardial cells. The matrix provides tensile strength to the tissue, governs the tissue's stiffness, and preserves the alignment of the myocardial cells. Abnormalities in the matrix's composition and concentration during dilation, hypertrophy and ischemic injury inhibit the function of the heart and may lead to heart failure.
Endogenous factors regulate the breakdown and/or re-establishment of collagen and other extra-cellular matrix components. These endogenous factors are diverse and their functions and structures are the subject of much research. The endogenous factors include a family of enzymes known as the matrix metalloproteinases. The matrix metalloproteinases catalyze a reaction breaking down the extra-cellular matrix. The enzymatic activity of the matrix metalloproteinases is countered by a set of proteins known as the tissue inhibitors of the matrix metalloproteinases (TIMPs). The TIMPs inhibit the enzymatic activity of the matrix metalloproteinases. The matrix metalloproteinase:TIMP ratio is typically around 1.1:1.0 in a normal heart. The ratio may be around 6:1 or 7:1 by the end stage of CHF. Research has shown that the interruption of matrix metalloproteinases with pharmaceutical agents reduces chamber dilation in animal models for CHF. Relatedly, this research has shown an overall increase in the collagen content due to the treatments.
In addition, the inhibition of matrix metalloproteinases and, presumably, the subsequent increase in collagen have been shown to result in the beneficial remodeling of treated diseased hearts. Interruption of matrix metalloproteinases with drug therapy has been shown to reduce chamber dilation in CHF animal models. However, drug therapy for inhibiting matrix metalloproteinases may present potentially serious problems. The systemic inhibition of the matrix metalloproteinases has been found to produce a variety of side effects, such as joint and muscle pain. Therefore, a need exists for a therapy that specifically targets the desired tissue or organ to be treated.
Another aspect of degenerative remodeling is ischemic cardiomyopathy. In ischemic cardiomyopathy, a loss of blood flow or ischemia to a portion of the heart muscle causes not just weakness or scarring to that portion, but subsequently a progression to chamber dilation and failure. The loss of blood flow may be the result of arteriosclerosis, other cardiac diseases, or injury, which can result in a partial or complete blocking of blood flow to a region of the heart. The limited blood flow may result in localized tissue death known as an infarction. The presence of an infarction weakens contraction in that region and therefore degrades the heart's performance. To compound the problem, the myocardial tissue adjacent to the infarction typically receives a reduced blood flow and, therefore, exhibits reduced contractility. The zone receiving the reduced blood flow is known as an ischemic zone. The ischemic zone further inhibits the hearts ability to contract. Further, the elevation of matrix metalloproteinases, reduction in TIMPs, and consequent degradation of collagen may play an additional role in ischemic cardiomyopathy. To improve cardiac output in patients with ischemic cardiomyopathies, there is a need to re-establish blood flow to the ischemic zones.
Re-establishing blood flow to the ischemic zone has been shown to improve cardiac function. Re-establishing blood flow may be accomplished through angiogenesis in which the body generates additional blood vessels in a particular region. Prior methods for re-establishing blood flow and rehabilitating the heart frequently involved invasive surgery such as bypass surgery or angioplasty. Other methods have used lasers to bore holes through the infarctions and ischemic zones to promote blood flow. These surgeries are complicated and dangerous. Therefore, a need exists for a safe non-invasive method for re-establishing blood flow.
As alternatives to surgery, various chemical and biological agents have been developed that promote angiogenesis. Genetic engineering has played a significant role in the development of many of these new agents. However, in practice, direct injection of these angiogenic agents fails to specifically target the ischemic zone. Further, injection of genetic material within a vector is a more biologically complex process and frequently suffers from a low transfection efficiency. In addition, the introduction of xenobiotics compounds can be dangerous. The compound itself may be toxic, virulent and/or allergenic. Therefore, a need exists for a therapy for promoting angiogenesis that is efficient and does not introduce xenobiotics into a patient. In addition, many of the drugs prescribed for CHF patients are primarily for palliative or symptomatic relief These drugs typically do not treat the underlying disease process of CHF and their use frequently results in serious or prohibitive side effects. Further, the drugs are typically administered systemically and therefore, impact the entire body not just the organ or tissue to be treated. Therefore, a need exists for a therapy capable of promoting overall remodeling without inducing unwanted side effects.
Atrial fibrillation is another serious condition in which degenerative tissue remodeling also plays a significant role. As in CHF and coronary ischemic disease, early theories on the cause of atrial fibrillation suggested that its causes may be multi-factorial, but the onset of degenerative tissue remodeling exacerbates atrial fibrillation.
The promotion of healing with electric current stimulation has been recognized in medicine for many years. Most commonly, electricity is used to promote bone union in fractures that have proven refractory to normal healing. The devices used have directly applied the current to the skin over the fracture. Alternatively, other devices use pulsed electromagnetic fields (PEMF) that do not require direct skin contact to promote healing.
Electrical stimulation of cardiac tissues has also been utilized to treat various conditions of the heart. Pacemakers provide electrical stimulation above the contraction threshold to treat various arrhythmias. Further, sub-threshold stimulation currents have been used to extend the cardiac tissue's refractory period in the treatment of tachycardia and to increase contractility in the cardiac muscle. However, sub-threshold stimuli have not been broadly applied to the heart and adjacent blood vessels to promote healing and tissue remodeling.
Providing electric current stimulation of ischemic zones on the heart has recently been shown to promote angiogenesis and further, electric current stimulation has been shown to increase collagen type I production in cultured cells. However, directly or indirectly applying electrical stimulation to the heart can be dangerous. There is a risk of inducing a depolarization of the cardiac tissue resulting in an unwanted cardiac contraction. Further, there is a risk of inducing a life-threatening arrhythmia. Therefore, a need exists to provide a method and apparatus that reduces the risks of providing an electrical stimulation to the heart to promote angiogenesis, to increase collagen type I production, to prevent the breakdown or degradation of extra-cellular matrix proteins, and to promote other aspects of beneficial remodeling.
One problem not addressed by prior methods is the inability to accurately assess the field strength generated in the region of the heart. Significant variation in body types, conductivity profiles and stimulation thresholds exist between patients. A particular stimulus level may be safe when applied to one patient, and yet that same stimulus may evoke an unwanted reaction from another patient. Thus, a need exists for a method and apparatus for measuring the field strength of a therapeutic current. Another problem is the artifact created by an applied stimulus, which may disrupt the sensing and activation of an implanted pacing or defibrillation device. The disruption could result in stimulation at a high-risk portion of the cardiac cycle, or an undesirable or unnecessary defibrillation shock. Thus, a need also exists for a method and apparatus that reduce the likelihood for disruption of an implanted pacing or defibrillation device.
The apparatus and method of the present invention meet the above needs and provide additional improvements and advantages that will be evident to those skilled in the art upon review of the specification and figures.